tbuckley/cabot-search huggingface dataset:
Standardization of toxicity related dose modification in oncology electronic health record (EHR).
Authors: Amit Sanyal, Daniel Wellner, James Thomas, Matthew Mattila
Journal: Journal of Clinical Oncology (2022)

e18616 Background: Inappropriate antineoplastic drug dosing can cause excessive toxicities or impaired efficacy. Chemotherapy dose delays and reduced dose intensity are common in community oncology practices[1]. Electronic tools can improve quality and safety of chemotherapy. Methods: A quality improvement project to standardize toxicity related dose modifications was initiated in January 2021. A dose modification section was created in BEACON (Epic Systems, Verona, WI) chemotherapy protocols. Dose modifications used in primary source studies were added to the protocols (Table, illustrative). An embedded link to relevant section of the study protocol allowed detailed review. Similarly, a link to the relevant CTCAE grading was embedded for reference. A user experience survey was conducted in August 2021 to evaluate adoption and perceived utility. Results: Dose modifications recommendations have been introduced in 104 protocols to date. Of the 70 survey respondents, there were 18 physicians and 5 advance practice providers, remainder being oncology nurses and pharmacists. Pre-implementation, 29% (8/27) of respondents whose role required performing dose modifications indicated using personal clinical judgement for hematological toxicity related dose modifications. 34% (9/26) did the same for non-hematological toxicities. Post-implementation, 87% respondents indicated awareness of the recommendations. 47% indicated that recommendations saved timed and 60% found these useful. 7.2% felt recommendations were impractical for clinical use. Conclusions: Embedding evidence-based dose modification recommendations into EHR based treatment protocols is feasible with widespread user adoption. References Denduluri, N., et al., Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices. J Natl Compr Canc Netw, 2015. 13(11): p. 1383-93. Illustrative Dose Modification Table. Reference Links 1. Grothey et al. Dose Modifications 2. CTCAE Grading. Refer to Reference Link for Detailed Instructions. Decrease Oxaliplatin and 5 FU one dose level for ANC&lt;1000, platelets &lt;50,000, Grade 4 diarrhea Decrease 5 FU one dose level for Grade 3 diarrhea, Grade 3 or 4 mucositis Decrease Oxaliplatin one dose level for Grade 2 neurotoxicity persisting between treatments, Grade 3 neurotoxicity resolving to &lt;/= Grade 2 between treatments Discontinue Oxaliplatin for Grade 3 neurotoxicity persisting between treatments, Grade 4 neurotoxicity.[Table: see text]
Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes
Authors: Silva A. Arslanian, Tamara Hannon, Philip Zeitler, Lily C. Chao, Claudia Boucher-Berry, Margarita Barrientos-Pérez, Elise Bismuth, Sergio Dib, Jang Ik Cho, David Cox
Journal: New England Journal of Medicine (2022)

The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes.In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed.A total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (-0.6 percentage points in the 0.75-mg group and -0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (-18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults.Treatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.).
Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): A post hoc analysis of sustained minimal residual disease (MRD) negativity from GRIFFIN.
Authors: Cesar Rodriguez, Jonathan L. Kaufman, Jacob Laubach, Douglas W. Sborov, Brandi Reeves, Ajai Chari, Rebecca Wang Silbermann, Luciano J. Costa, Larry D. Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Andrzej J. Jakubowiak, Robert Z. Orlowski, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S. Lin, Paul G. Richardson, Peter M. Voorhees
Journal: Journal of Clinical Oncology (2022)

8011 Background: In the primary analysis of the phase 2 randomized GRIFFIN study, DARA + RVd (D-RVd) improved the stringent complete response (sCR) rate by end of consolidation for transplant-eligible NDMM (42.4% vs 32.0%; 1-sided P = 0.068). With longer follow-up (median, 38.6 mo), D-RVd vs RVd improved MRD-negativity (10 –5 ) rates in clinically relevant subgroups (ISS stage III, 71% vs 36%; high cytogenetic risk, 44% vs 29% [del17p, t(4;14), or t(14;16)]; revised high cytogenetic risk, 55% vs 32% [del17p, t(4;14), t(14;16), t(14;20), or gain 1q]). Here we present a post hoc analysis of sustained MRD negativity (median follow-up, 38.6 mo) in the same subgroups and in patients (pts) with ≥CR. Methods: Transplant-eligible NDMM pts were randomized 1:1 to 4 D-RVd/RVd induction cycles, ASCT, 2 D-RVd/RVd consolidation cycles, and 2 years of maintenance therapy with lenalidomide (R) ± DARA. For induction/consolidation (21-day cycles), pts received R (25 mg PO Days [D] 1-14), V (1.3 mg/m 2 SC D1, 4, 8, 11), and d (40 mg PO weekly) ± DARA (16 mg/kg IV D1, 8, 15 of Cycles 1-4 and D1 of Cycles 5-6). In maintenance (28-day cycles), pts received R (10 mg PO D1-21; if tolerated, 15 mg in Cycles 10+) ± DARA (16 mg/kg IV Q8W/Q4W or 1800 mg SC per protocol amendments). The primary endpoint was sCR rate by end of consolidation. Results: The following features were balanced among randomized pts (D-RVd, n = 104; RVd, n = 103): high cytogenetic risk (16; 14), revised high cytogenetic risk (42; 37), gain 1q (34; 28), and ISS stage III (14; 14). Sustained MRD-negativity rates at 10 –5 lasting ≥6 and ≥12 months were higher for D-RVd vs RVd among all high-risk subgroups (Table). D-RVd was superior to RVd for rates of sustained MRD negativity lasting ≥12 months for pts with ≥CR (53.7% vs 20.3%) and sCR (59.1% vs 17.4%; Table). Among all pts with sustained MRD negativity, only 1 D-RVd pt subsequently had disease progression, and 1 RVd pt died. Additional data on MRD at 10 –6 and PFS will be presented. Conclusions: MRD data in GRIFFIN show that the addition of DARA to RVd induction/consolidation and R maintenance may lead to durable MRD-negativity (10 –5 ) rates in pts with transplant-eligible NDMM with high cytogenetic risk, ISS stage III, and those who achieve ≥CR or sCR, however larger studies are needed. Clinical trial information: NCT02874742. [Table: see text]
IMG-15. Radiomic Profiling of Pediatric Low-Grade Glioma Improves Risk Stratification Beyond Clinical Measures
Authors: Anahita Fathi Kazerooni, Sherjeel Arif, Debanjan Haldar, Rachel Madhogarhia, Ariana Familiar, Sina Bagheri, Hannah Anderson, Jeffrey B Ware, Arastoo Vossough, Phillip B Storm, Adam C Resnick, Christos Davatzikos, Ali Nabavizadeh
Journal: Neuro-Oncology (2022)

Abstract PURPOSE: Treatment response is heterogeneous among patients with pediatric low-grade glioma (pLGG), the most frequent childhood brain tumor. Upfront prediction of progression-free survival (PFS) may facilitate more personalized treatment planning and improve outcomes for the pLGG patients. In this work, we explored the additive value of radiomics to clinical measures for prediction of PFS in pLGGs. We further sought associations between the derived risk groups and underlying alterations in key genomic and transcriptomic variables. METHODS: Quantitative radiomic features were extracted from pre-operative multi-parametric MRI scans (T1, T1-post, T2, T2-FLAIR) of 96 patients with newly diagnosed pLGG (median age, 8.59, range, 0.35-18.87 years; median PFS, 25.23, range, 3.03-124.83 months). Multivariate Cox proportional hazard’s (Cox-PH) regression models were fitted using 5-fold cross-validation on a training cohort of 68 subjects and tested on 28 patients. Three models were generated using (1) only clinical variables (age, sex, and extent of tumor resection), (2) radiomic features, and (3) clinical and radiomic variables. The dimensionality of radiomic features in Cox-PH models was reduced by applying Elastic Net regularization penalty to identify a subset of variables that are most predictive of PFS. The patients were then stratified into three groups of high, medium, and low-risk based on model predictions. RESULTS: Cox-PH modeling resulted in a concordance index (c-index) of 0.55 for clinical data, 0.65 for radiomics, and 0.73 for a combination of clinical and radiomic variables, highlighting the additive value of radiomics to the readily available clinical information in prediction of PFS. Radiogenomic assessments revealed significant differences in expression of BRAF, NF1, TSC1, ALK (p&amp;lt;0.01), and RB1 (p&amp;lt;0.05) genes in the high-risk group, compared to the medium and low-risk groups. CONCLUSION: Our results demonstrate the value of integrating radiomics with clinical measures to improve risk assessment of patients with pLGG through improved pretreatment prediction of PFS.
MODL-09. Exploring the role of Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) inhibition as a potential therapeutic intervention in medulloblastoma
Authors: Clay Hoerig, Ashley Plant-Fox, Kaijun Di, Javi Lepe, Christopher Douglas, Naomi Lomeli, Bhaskar Das, Daniela Bota
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Brain tumors are the second most common type of pediatric cancer and the leading cause of all cancer-related deaths in children. Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor and has a five-year overall survival ranging from 40-75%, depending on the patient’s age and other prognostic features. There are various anti-cancer therapies against medulloblastoma, but the treatment of recurrent and refractory disease remains a challenge. As a result, the need for new and novel therapies remain a top priority. One area of interest in CNS tumors are targets within mitochondria. Magmas overexpression has been reported in multiple types of metabolically active tissue and cancer cells, including prostate cancer, pituitary adenoma, and glioma. Some new data suggest that specific subgroups of medulloblastoma may also overexpress Magmas. This ongoing study aims to examine whether Magmas inhibition by compound “BT9” could be beneficial in the treatment of medulloblastoma. METHODS: We continue to study the ability of a Magmas inhibitor (BT#9) as a therapeutic agent in stable medulloblastoma cell lines and patient-derived primary cultures by performing MTT assays, tunnel assays, flow cytometry, migration assays, and invasion assays. RESULTS: Similar to the adult GBM studies, Magmas inhibition by BT#9 had signiﬁcant cytotoxic eﬀects, causing both decreased cell proliferation, increased apoptosis, and blocked cell migration in medulloblastoma cell lines DAOY, D283, and D425. IC50s determined for each during different time points demonstrated an average range 2-5μM compared to the average range seen in adult glioblastoma cell cultures which could range up to 10 μM. These findings suggest that the inhibition of Magmas could potentially optimize clinical outcomes in recurrent/refractory medulloblastoma and warrants further investigation. Our future studies will include the determination of IC50s for primary cell cultures and in vitro testing with patient-derived xenograft models.
Real-world data comparing FOLFIRINOX versus gemcitabine nab-paclitaxel as first-line treatment of metastatic pancreatic ductal adenocarcinoma patients in the United States.
Authors: Avital Klein-Brill, Shlomit Amar-Farkash, Gabriella Lawrence, Eric Andrew Collisson, Michael Jordan Fisch, Dvir Aran
Journal: Journal of Clinical Oncology (2022)

e16271 Background: The common first-line therapies for metastatic adenocarcinoma of the pancreas (mPC) are FOLFIRINOX and gemcitabine plus nab-paclitaxel (Gem-Nab-P). However, these treatments have not been directly compared in a clinical trial and comparative real-world data analyses on their effectiveness are limited. Using real-world data, we evaluated the impact on overall survival and post-treatment hospitalizations of 1L FOLFIRINOX vs. Gem-Nab-P in individuals with mPC. Methods: We performed a retrospective cohort study of 1L treatment of patients with mPC between 1/2015 and 6/2020, utilizing administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (rwOS) was defined as time from diagnosis to death. Inverse probability of treatment weighting (IPTW) was used to adjust for age, ECOG, Socioeconomic index (SDI), comorbidity, metastatic sites and pre-treatment. Median rwOS was estimated using the weighted Kaplan-Meier method. Results: Our cohort included 1,102 1L mPC patients, 566 (51.4%) treated with FOLFIRINOX (F), and 536 (48.6%) treated with Gem-Nab-P (GNP). F-treated patients were generally younger, with better performance status (ECOG PS), fewer comorbidities and living in regions with higher socioeconomic index. Following adjustments, the Median rwOS was 9.28 and 6.82 months for F-initiated patients and GNP, respectively (p-value = 2.5e-07). This survival benefit of F was observed among all sub-groups, including different ECOG PS, ages, socioeconomic index and metastatic sites. F-treated patients also had fewer post-treatment hospitalizations (p-value=0.027) and lower post-treatment costs (p-value=0.00004). Conclusions: Our retrospective cohort study demonstrated that FOLFIRINOX is associated with improved survival of approximately 2 months over Gem-Nab-P and is also associated with fewer post-treatments complications. A randomized controlled trial comparing these first line treatments is warranted to test the survival and post-treatment complications benefit of FOLFIRINOX over Gem-Nab-P.[Table: see text]
Systematic Cross-Biospecimen Evaluation of DNA Extraction Kits for Long- and Short-Read Multi-Metagenomic Sequencing Studies
Authors: Jacqueline Rehner, Georges Pierre Schmartz, Laura Groeger, Jan Dastbaz, Nicole Ludwig, Matthias Hannig, Stefan Rupf, Berthold Seitz, Elias Flockerzi, Tim Berger, Matthias Christian Reichert, Marcin Krawczyk, Eckart Meese, Christian Herr, Robert Bals, Sören L. Becker, Andreas Keller, Rolf Müller
Journal: Genomics Proteomics & Bioinformatics (2022)

High-quality DNA extraction is a crucial step in metagenomic studies. Bias by different isolation kits impairs the comparison across datasets. A trending topic is, however, the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases. We thus collected bile, stool, saliva, plaque, sputum, and conjunctival swab samples and performed DNA extraction with three commercial kits. For each combination of the specimen type and DNA extraction kit, 20-gigabase (Gb) metagenomic data were generated using short-read sequencing. While profiles of the specimen types showed close proximity to each other, we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits. No kit outperformed all selected kits on every specimen. We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit. Depending on the specimen, our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution, but DNA-based identification is superior to identification by mass spectrometry. Finally, long-read nanopore sequencing confirmed the results (correlation coefficient > 0.98). Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.
Real-world utilization of ctDNA in the management of colorectal cancer.
Authors: Kristin M. Zimmerman Savill, Danielle Gentile, Yolaine Jeune-Smith, Andrew J. Klink, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2022)

3075 Background: The utilization of circulating tumor DNA (ctDNA) as a non-invasive biomarker for the detection of minimal residual disease, prediction of recurrence in the post-operative setting, and real-time monitoring of treatment efficacy has the potential to vastly improve the care and outcomes of patients with colorectal cancer (CRC). In August of 2020, ctDNA testing first gained approval for use in solid tumors and its prognostic benefit after curative intent surgery has been demonstrated to exceed that of prior standard of care clinicopathological criteria in CRC patients. The comprehensive integration of validated ctDNA approaches into the routine clinical care of patients with CRC would not only fundamentally change how risk of recurrence is assessed but could also reduce treatment with unneeded/unwarranted toxic therapies and allow for earlier recognition and treatment in cases with a high risk of relapse. This survey-based study aimed to evaluate the utilization of ctDNA testing in the management of CRC among practicing community oncologists in the U.S. Methods: Questions related to ctDNA utilization for patients with CRC were presented to community oncologists during a virtual meeting held in July 2021. Descriptive statistics were used to analyze the results. Results: Of 55 participating oncologists geographically distributed across the U.S., 49% indicated not using ctDNA to make treatment decisions in CRC. A proportion of physicians reported using ctDNA to detect recurrence (27% of physicians); make decisions around post-resection adjuvant therapy (25%); monitor disease progression/relapse (18%); and track tumor resistance during treatment (9%). The most frequently cited barriers to ordering ctDNA testing for patients with metastatic CRC were reimbursement issues (reported by 56% of oncologists), insufficient clinical evidence (46%), and limited familiarity with ctDNA use (28%). Oncologists reported that the following would increase their utilization of ctDNA testing: more clinical evidence of the utility of ctDNA (reported by 66% of physicians), increased education on methodology (60%), more education on the use of ctDNA (57%), more financial aid and reimbursement support for patients (49%), more decision support tools (47%), and better communication between physicians and vendors (26%). Conclusions: These findings demonstrate limited adoption of ctDNA testing by community oncologists in the care of CRC patients. Insufficient demonstration of clinical utility, limited familiarity with methodology, and reimbursement issues were cited as barriers to uptake. Education for community oncology providers about ctDNA testing and its demonstrated clinical utility, and increased financial support for patients may improve its utilization and adoption in CRC to improve patient outcomes and care.
Record breaking heat hits India and Pakistan
Authors: Alison Shepherd
Journal: BMJ (2022)

Fractures that split the humeral head are extremely rare, and usually, the split part is posteriorly dislocated. However, in our case, the split part was anteriorly dislocated and trapped between the anterior glenoid and the subscapularis muscle. In this case, the acquisition of preoperative CT results was vital to plan the exposure and reduction strategies. Open anatomic reduction and internal fixation should be considered as the first treatment of choice in young active adults.
Event-Free survival after 68Ga-PSMA-11 PET/CT in recurrent Hormone-Sensitive Prostate Cancer (HSPC) patients eligible for salvage therapy
Authors: F. Ceci, G.R. Rovera, G.C. Iorio, A. Guarneri, V. Chiofalo, R. Passera, M. Oderda, S. Dall’armellina, V. Liberini, S. Grimaldi, M. Bellò, P. Gontero, U. Ricardi, D. Deandreis
Journal: European Urology (2022)